Micro Viruses Test Questions – Flashcards

1. 20-33nm
2. Icosahedral
3. ssRNA(+polarity) 
4. No lipid envelope
5. Rhinoviruses-unstable below pH 6, Enteroviruses stable at pH3-9
6. Ususally transmitted in an oral to fecal route. Occasionally you will have a viremia in which you can have a primary spread through the bloodstream to the target tissue, or a secondary viremia in which there is a spread globally. Entry into cell is always cellular receptor mediated. 

1. Coxsackie A viruses(A24 and 28), Enterovirus 70 
2. Rapid onset of watery discharge, foreign body sensation, burning and photophobia. 

• Coxsackie A16, occasionally other Coxsackie A viruses and Enterovirus 71
• Symptoms: Mild fever, sore throat, fatigue, loss of appetite, vesicular lesions in the hands,feet and mouth.

1. Coxsackie B viruses 
2. Sudden onset of fever and sever epigastric or thoracic pain. Diseases usually lasts from 2-4 days but may relapse and symptoms may recur for several weeks.

1. Coxsackie Viruses 
2. Symptoms: Sudden onset of fever, sore throat, headaches, anorexia, vesicicular ulcerated lesions usually occuring in the back of the throat around the tonsils and rear portion of the palate.  

1. (90-95%) usually subclinical manifestations, virus is recovered from throat and stool, the pt is asymptomatic. 
2. (4-8%) Febrile undifferentiated disease, occasional respiratory infection, influenza like illness; gastroenteritits
3. Aseptic meningitis (nonparalytic polio) stiffness in neck and back (CNS infiltration) lasts 2-10 days with rapid and complete recovery. 
4. (.1-2%)Initial non-specific febrile illness. Paralysis is variable(only isolated muscle groups or extensive paralysis). Symptoms: affects lower limb and larger muscle groups more often and results in asymmetric flaccid paralysis. Bulbar paralysis-involves the cranial nerves, medulla, respitory compromise and result in death in 5%. Recovery is slow (2 years for 100%). Complications: Residual paralysis. 
5. 10-40 years after recovery from the paralytic attack. Fatigue, muscle weakness, sleeping probs, breathing difficulties, joint pain, cold sensitivity. Not life threatening. Results from the death of individual nerve terminals that remain from the initial attack. No treatment is successful. 

Virus entry-->alimentary canal, mutiplies locally (tonsils and peyer's patches). Invasion and multiplication occurs in the SI and multiplication occurs in the Mesenteric LN.;

;

Primary viremia can occur in the bloodstream.;

CNS: Invasion and multiplication, intraneural spread occurs and the motor neves are destroyed which leads to paralysis.

;

The virus is present in the pharynx 1 to 2 weeks after infection, and excreted in the stools for several weeks.

Recptor binding and entry. Needs to get into the vesicle and acidify. Polio virus only makes ONE protein. Doesn't require a cap in order to undergo transcription. Requires a protease in order to limit products. RNA-dependent RNA replication on vesicles. Encapsulation and Exit. (1 enter:1000 exit) 

RNA: Enters the cell as a genomic (+) sense RNA, (-) sense RNA is what is encapsulated.  

1. Most common cause of GI disease in infants and children claiming the lives of 500,000 children a year mostly in Asia and Africa. Sero-conversion by 2-3 years, infants less than 6 mo. don't get infected due to transplacental transfer of maternal antibody. Fecal/oral transmission. Disease is seasonal late fall to spring.;
2. Genome: 8 dsRNA segments encoding 12 genes. No envelope-three layered capsid and contains multiple antigenic groups A-E. Group A is the most common cause of human disease. Co-infection leads to;re-assortment;of segments (know that assortment occurs b/t translation and assortment, see pg. 56).;3 capsids: inner-VP2, middle-VP6 (subgroup antigen A-E), outter-VP4/VP7 (both are neutralization antigens). Activated by trypsin in the GI.;
3. Attach and infect enterocytes in villous epithelium of SI. Causes death of cells at the villious tips. Releases the enterotoxin NSP4 which causes Ca ion transport into the enterocyte and activates the enteric nerves. Cell loss results in the loss of intestine permeability.;
4. mucosal, humoral immunity ;(neutralizing antibodies directed against VP4 and VP7)is key, early IgM in duodenal fluid and serum. IgA and IgG present 1-4 months, IgA declines and susceptibility returns but with less severe disease which may hint at cell memory. Seems to be T-independent immunity. May result in viremia.;
5. Rotashield-live, attenuated reassortment virus (from both monkey and human viruses). Resulted in intussusception, fever, vomiting, etc.;

Rotateq-live,attenuated-bovine reassortment

Rotarix- live attenuated single human strain

;

;

1. Major cause of gastroenteritits(GE) in school aged children and adults. ;90% of food-related outbreaks of GE in the US. Infections in the very young and elderly can require;hospitalization. Short incubation time (8hrs-2days)from exposure to disease. 2-3 days of diarrhea with vomiting. Virus is shed in stool. fecal to oral transmission, food borne or person to person.Cannot grow in culture. Has a great genetic diversity. 20% of population doesn't have HBGA receptors and therefore have a resistance to Norovirus. 
2.  Low infectious dose <100 viral particles. CAN occur with reinfection. Externally stable! Nonenveloped, ssRNA, (+) sense genome. Contains its own viral protease(much like polio) and RNA-dependent RNA polymerase, which are both targets for antiviral therapies.  
3. Loss of epithelium, inflammation of mucosa, villus shortening, poor absorption of water and nutrients.

1. One of the leading causes of acute gastroenteritis in infants. Clinically important in the elderly and the immunocompromised. 
2. (+)ssRNA, Spherical virion with no envelope and small spikes which make it look star-like. Can replicate in human colon carcinoma cell line. Infects many animal species. 
3. Incubation time 1-4 days, ilness 4 days-diarrhea, vomiting, abdominal distention, and mild dehydration. Immunity dependent on IgA. 

1. Original isolate from adenoid tissues, latent virus in adenoids and the tonsils. rare re-infection. Family common antigen. Can also result in ocular infections (epidemic keratoconjunctivitis, pharyngoconjunctival fever). Incubation 3 to 10 days, diarrhea lasts 6 to 9 days, may have vomiting and fever. 
2. dsDNA genome, and not enveloped. Spread via fecal/oral route for some and respiratory for others. Frequently causes unapparent respiratory infections. Stimulates cells to enter S phase because it needs to utilize the cells DNA synthesis mechanisms/machinery. Viral proteins bind cellular growth supressor proteins: Rb and p53. 
3. Excess virus penton spike fiber is released from cells which disrupts adhesion junctions. 

1. Picornavirus.Transmitted via a fecal to oral route, also via shellfish. No chronic infection state is seen. The mechanism for transmission is generally unknown. 
2. Has a single Serotype (Can make effective vaccines....boo-yah take that Hep A). Protective antibodies develop in response to infections and facilitates lifelong immunity. Has ssRNA which is attached to VPg. mRNA is translated into 1 polyprotien which is cleaved to form mature products. Enters via a receptor which is enhanced in the liver. 
3. Usually takes an average of 30 days in order to manifest-range is 15-50 days. Usually asymptomatic for 2-6 weeks. Adolescents  usually present with jaundice mostly.
4. Purified product inactivated with formalin, Adsorbed to aluminum hydroxide adjuvant,  Cell culture adapted virus grown in human fibroblasts. Vaccination indicated for infants, people working with HAV incidence, street drug users, homosexual sexually active males. 

1. Enteric virus of the calicivirus family. Most outbreaks are associated with contaminated drinking water. Person to person transmission is extremely rare. The cases seen in the US are usually the result of travel. 
2. (+) sense ssRNA virus, icosahedral 

1. Structure is not as uniform as A or E. Infants that are infected have a 90% chance for chronic infection (need to vaccinate infants early in order to improve community health). Can be sexually transmitted, and has a high concentration in blood, serum, and wound exudates. Moderately seen in genital secretions. 90% resoultion, 1% fulminant hepatitis, 9% has HBsAg in blood for over 6 months. May lead to chronic hepatitis (persistant or active) which may lead to cirrhosis or hepatic cell carcinoma (long latency). For HCC: virally-encoded X protein linked to signal transduction cascades that can be oncogenic. X decreases p53 activity as well as other key pathways. The presence of Δ factor can influence the outcome of HBV infection. 
2. DNA Genome (Hepadnavirus), circular DNA and partly ds DNA.  
3. Genome enters and DNA synth occurs to from fully ds DNA--> Genome to the nucleus where its transcribed into mRNA-->mRNA translation in the cytoplasm--> mRNA is "reverse-transcribed" to ssDNA, DNA is made partially ds again-->Encapsulation-->Virion is released as well as subviral particles. (it is good to note the viral DNA can also intergrate into the hosts chromosome and remain in the cell) 
4. Dane particles are non-infectious antigens surrounding the HepB particle. It is immunogenic but not infectious.

1. Viriod-can only grow in Hepatitis B-infected cells.
2. small RNA, copied by host RNA Polymerase II, catalytically active active "ribozyme" that processes itself, encodes one antigen, becomes packaged in Hep B sAg
3. Coinfection (at the same time)-severe acute disease, low risk of chronic infection. Superinfection(subsequent to HBV infection) usually develop chronic HDV infection, high risk for chronic liver failure.  

1. Large genome: 100-250kbp, dsDNA, enveloped and liable in the enviornment. Entry into cell is accomplished via the lipid envelope proteins.Can survive 2 hrs on the skin and 4hrs on plastic surfaces. α-HSV (HSV1 and 2) and Varicella Zoster Virus(VZV) gamma and beta in lecture 48. Alpha establish latency in sensory ganglion/neurons. Virus may seed to other organs (adrenal glands, liver, CNS). 
2. Encodes enzymes involved in nucleotide metabolism, DNA synthesis (DNA Polymerase), protein kinase (all HSV have protein kinase). Viral DNA and capsid assembled in nucleus and the rest put together in the virion. Two life cycles: lytic replication and latency
3. Lytic infection: 1)Binding 2)transport of capsid to the nucleus 3) Viral vhs (from tegument) begins to degrade host mRNA 4) Viral transcription factor VP16localizes to the nucleus to initiate transcription 5)Viral DNA circularizes 6)HSV alpha genes transcribed by host RNA polymerase II 7) some of these alpha genes activate beta gene transcription 8) some beta gene products are required for viral DNA synth. 9)Viral DNA synthesis triggers the expression of gamma viral genes 10)Gamma genes are structural components of the virion 11) Viral DNA is packaged into the capsid 12)Filled viral capsid buds through the host membranes to form a mature virion that exsists from the cell. 
4. Circular viral DNA is associated with host nucleosomes and is maintained as an episome. VERY LITTLE VIRAL EXPRESSION. Occasional reactivation for the life of the host. Triggered via UV rad, stress, other viral infections, physical trauma(damage of neurons). HSV-1 is latent in the Trigeminal ganglia, HSV-2 is latent in the sacral ganglia. Latency is associated with mRNAs called Latency Associated Transcripts(LATs) which are never translated into protein, and function to repress HSV gene expression. Frequency of reactivation is high.  
5. Oral-Oral, skin -skin, genital-genital and a mix of all the above. Viral shedding occurs in the saliva, oro-facial lesions and secretions, tears. HSV-1 mouth, HSV-2 more commonly seen in the genital tract.
6. Target replicating virus only! Acyclovir is a nucleoside analogue that competes with dGTP for viral DNA polymerase. The ACV-PPP is bound irreversibly, which ties up the polymerase. Varicella zoster vaccine is the only herpesvirus vaccine that is clinically licensed-live attenuated virus.
7. Primary oral-facial infection: herpes gingivostomatitis or pharyngitis.                           Recurrent oral-facial infection: herpes labialis            Neonatal herpes:  Inoculation during birth is the most common, if during pregnancy-birth defects. CNS affected. Mortality is high even with acyclovir treatment. May not have the skin lesions. Survivors have a high incidence of neuro abnormalities. Need to treat mother prior to birth of the child.               Herpes encephalitis,                                           keratitis and conjunctivitis-w/ is the leading cause of blindness                                                Herpes whitlow-hand dermatitis-gloves do not prevent the transmission. (DAMN HERPES.....YOU SCARY!)        
8. Vesicles at the site of inoculation , culture of the virus, immunofluorescence using antibodies against HSV antigens, PCR assays, serology to determine infection status. 

1. Humans the only reservoir, causative agent of chickenpox: incubation period of 10-21 days. P2P contact causes spread even before skin lesions. Can be transmitted via aerosolization of both the lesions and the respiratory tract. Viral replication occurs in the T cells, epi, and endothelial cells. Primary infections may involve CNS, but neurological abnormalities after treatment are uncommon.
2. Latency in the sensory nerve ganglia, many ganglia are involved due to the systemic spread of the the virus. Gene products are actively transcribed within the latently infected neurons. 
3. Chickenpox. Blisters, malaise, fever. Asprin causes liver damage (Reye's syndrome). Secondary skin infections and pneumonia is more common in adults. Neonatal VZV is rare and associated with multiple devo abnorms. ;Herpes zoster: reactivation of a latent VZV from a single sensory ganglia. Postherpetic neuralgia is a significant complication of zoster-severe pain which mimics appendicitis or a heart attack. Pain can last for months. Antivirals have no effect.;
4. acyclovir, VZV immune globulin. VZV vaccine- live attenuated, reduces the severity of primary infection. Oka strain establishes lifelong latent infection which may cause mild symptoms. Can be contraindicated in immunocompromised pts or pts with immunocompromised siblings.

;

1. Many viruses that infects insects, fish, and man. inserts into host cell chromosome and can activate or inactivate genes;;;cancer (if genes are involved with growth control). Acquire mutation via replication and recombination.;
2. Best means to classify these viruses is via sequence;comparison. There are seven groups of RVs in total which are placed into Simple and Complex categories.;
3. Enveloped with env protein in membrane. Capsid is composed of structural proteins (gag gene); Matrix, Capsid(CA), Nucleocapsid, Protease. Has 2 compies of (+) ssRNA genome. Virus is diploid. CA-p24, TM-(gp41), SU- gp120.
4. The genome has gag, pol, and env segments. Proteases cleaves these groups into constitutive portions.;

;

1. Virus binds to cellular receptor. For HIV these receptors is CD4/CCR5. Others are aa transporters, LDL-like receptors and others.;
2. Viral envelope fuses either with the membrane either at the cell surface or in the endosome after endocytosis. *currently two antivirals to this step*. Genomic RNA is only partially uncoated at this pt. , remains in a protein particle. RT, IN, and some gag proteins remain associated. Needed to convert ssRNA--> dsDNA(via RT), nuclear import (HIV) and integration. NO TRANSLATION AT THIS PT. 

3. Integrated provirus is longer than the template RNA, and has U3 and U5 duplicated at the ends to form Long Terminal Repeats (LTR). Process of Reverse Transcription: ssRNA-->dsDNA

Reverse Transcriptase (RT), carried in with the virion

Preforms both processes:

RNA-dep. DNA polymerase (RNA--> ssDNA)

DNA-dep. DNA polymerase (ssDNA-->dsDNA) 

The polymerase is very much error prone, ~5 error per genome. This is why retroviruses have hella' evolution to drug resistance. 

RT target fro AZT

4. Integration- carried out via integrase which is brought in by the virus and remains associated with the dsDNA. Many retroviruses require a dividing host cell, as they cannot breech the nuclear membrane;however, HIV enters via nuclear pores.

Integrase is specific for the U3 and U5 sequences at the ends of the dsDNA. 

Intergration rxn is not specific for host sequences. Insertion is random. 

Once there is integration, the virus is a PERMANENT resident of the host. 

5. U3 has signals which are recognized by cell's transcription/poly A machinery. Only the 5' LTR is transcriptionally active. 

Organization of the LTR- U3 has binding sites for cellular transcription factors required for a high level of RNA synthesis. The specturm of proteins that bind influences which tissue/cells retroviruses is active in. 

6. All RNAs are polyadenylated, some must be spliced to generate env mRNA, but majority remain at full lenth to serve as gag-pol mRNA and as genome for progeny virions.

Three fates: 

Full length RNA--> genomic RNA

Full length RNA--> gag-pol mRNA

RNA splicing--> env mRNA

7. Most abundant protein is gag and gag-pol, made as a polyprotein from full length RNA. The cleavage by PR occurs OUTSIDE of the cell. 

env protein is made from spliced mRNA on ER-bound ribosomes, moves thru ER-golgi, is inserted into the plasma membrane. The cleavage of the precursor gp160 occurs via a cellular protease in the golgi 

8.Packaging- if an unspliced RNA contains the Phi signal, then it is packaged. 

Budding- Viral gag and gag-pol polyproteins recruit RNA and assemble under the cell surface. gag protein interacts with the env, and buffing occurs as the particle forms. 

Maturation- proteolysis of gag and gag-pol by PR occur AFTER budding. Viral particles still form and bud if proteolysis is inhibitedm but the subsequent viruses are not infectious. This is the basis of HIV PR inhibitors. 

1) non-acute or slow tumor viruses. Tumors take 6 mo to a year to form. No transfomation in cellular culture. No oncogenes, however tumors are caused by the activation or inactivation of host genes. ex. promoter insertion or enhancer insertion. 

2)acute- tumors within weeks, causes tissue cultur to become transformes or cancer-like . Oncogene is present. Infection introduces the cancer causing agent thus there is a rapid tumor onset. the oncogene replaces on or more viral genes.